We propose in vitro studies of the kinetics of formation of native three- dimensional structure in proteins, to find physiologically feasible general conditions for rapid structure formation, and to obtain information on the mechanism(s) of the self-assembly process. We will determine the identity and distribution of disulfide cross- linked intermidiates at various stages in the regeneration of reduced, disorganized proteins. Limited proteolysis followed by column chromatographic separations will make it possible to separate disulfide- containing peptides, which will be identified by amino acid composition. The pattern of distribution of disulfides provides a discriminant between a random search assembly process and a process inititated by nucleation followed by limited search of structures. Employing the three-dimensional structural results from X-ray crystallographic studies, we will attempt to devise new generalizations on protein structure suggested by and consistent with the outcome of the experimental work outlined above.